Preparation of fatty acid amides from nitro-nitrosoalkanes and nitroalkanone oximes

ABSTRACT

FATTY ACID AMIDES, SUCH AS VALERAMIDE, ARE PREPARED BY THE REACTION OF A 1-NITRO-2-NITROSOALKANE OR A 1-NITROALKANONE-2 OXIME WITH AN ANHYDROUS MINERAL ACID, SUCH AS SULFURIC OR PHOSPHORIC ACID, AT INTERMEDIATE TEMPERATURE OF, FOR EXAMPLE, ABOUT 70*C. FOR RELATIVELY SHORT CONTACT TIMES. THE LOWER FATTY ACIDS, SUCH AS ACETIC ACID, ARE USEFUL AS SOLVENT MEDIUMS.

United States Patent US. Cl. 260-404 Claims ABSTRACT OF THE DTSCLOSUREFatty acid amides, such as valerarnide, are prepared by the reaction ofa 1-nitro-2-nitrosoalkane or a l-nitroalkanone-Z oxime with an anhydrousmineral acid, such as sulfuric or phosphoric acid, at intermediatetempera tures of, for example, about 70 C. for relatively short contacttimes. The lower fatty acids, such as acetic acid, are useful as solventmediums.

This invention relates to the preparation of fatty acid amides fromcertain nitro-nitrosoalkanes and nitroalkanone oximes.

In accordance with the invention, a fatty acid amide having from 2 to 24carbon atoms can be prepared by reacting at least one l-nitroalkanehaving from 3 to 25 carbon atoms selected from the group consisting of a1- nitro-2-nitrosoalkane having a hydrogen atom on the beta carbon atomand a l-nitroalkanone-Z oxime with a mineral acid selected from thegroup consisting of sulfuric and phosphoric acids in a substantiallyanhydrous reaction medium comprising said mineral acid, under reactionconditions including a temperature of from 60 C. to 160 C.

The charge stock can be any l-nitroalkane selected from the groupconsisting of a 1-nitro-2-nitrosoa1kane having a hydrogen atom on thebeta carbon atom or a l-nitroalkanone-2 oxime. The l-nitroalkanesuitably has from 3 to 25 carbon atoms and preferably has from 4 to 18carbon atoms.

The monomeric 1-nitro-2-nitrosoalkanes have the formula:

where R is a saturated alkyl radical having from one to 23 carbon atoms.

The preferred l-nitroalkanone-Z oxime compounds can be represented bythe general formula:

where R is a saturated alkyl radical having from one to 23 carbon atoms.

Thus, the 1-nitroalkanone-2 oxime compounds are really isomers of thel-nitro-2-nitrosoalkanes defined above. The 1-nitro-2-nitrosoalkanesdefined above dimerize through the nitrogen atom of the nitroso groupand the dimers have the formula:

where R is as defined above. By a 1-nitro-2-nitrosoalkane in thisapplication is meant either the monomeric 1- nitro-Z-nitrosoalkanedefined above or the dimeric nitronitrosoalkanes defined above.

These dimeric nitro-nitrosoalkanes are calledbis(l-nitro-2-nitrosoalkanes) in the art. It is understood by those withordinary skill in the art that nitrosoalkanes dimerize through the Natom of the nitroso group. Such terminology is used, for example, inUnited States Pat. No. 3,379,710 to Alan F. Ellis; United States Pat.No. 3,009,- 965 to Moeller et al.; and in two articles by John F. Brown,Jr. entitled The Infrared Spectra of Nitro and Other Oxidized NitrogenCompounds and The Reaction of Nitric Oxide with Isobutylene published inthe Journal of the American Chemical Society, vol. 77, pages 63416351,and volume 9, pages 2480-2488, respectively.

The 1-nitro-2-nitrosoall anes can be prepared by any suitable proceduresuch as that disclosed in United States Pat. No. 3,379,710 to Alan F.Ellis issued on Apr. 23, 1968.

The l-nitroalkanone-Z oxime can be prepared by isomerizing the1-nitro-2-nitrosoalkanes. The isomerization of thel-nitro-2-nitrosoalkanes preferably occurs in the presence of a solventcatalyst, such as glacial aceti acid, as more fully described in mycopending United States Ser. No. 782,447, filed concurrently herewithand assigned to the same assignee as the subject file.

Suitable charge stocks, therefore, include the monomeric forms of thel-nitroalkane charge stocks, namely, the 1-nitro-2nitrosoalkanes and the1-nitroalkanone2 oximes in addition to the dimeric1-nitro-2-nitrosoalkanes known in the art as thebis(1-nitro-2-nitrosoalkanes).

It is believed, although it is not certain, that the reaction to formthe desired fatty acid amide proceeds through the monomeric form of thel-nitroalkanes, and thus the monomeric 1-nitro-2-nitrosoalkane and1-nitroalkanone-2 oxime forms of the charge stock are preferred.Additionally, the dimeric form of the 1-nitro-2-nitrosoalkanes is asolid, while the monomeric and oxime forms tend to be liquid and arethus easier to disperse in the reaction medium. This feature isimportant since the reaction to form the amide is highly exothermic andresults in gas evolution and ease of dispersion of the charge stock inthe reaction medium aids in temperature control and overall smoothnessof the reaction. However, the 1-nitro-2- nitrosoalkane is usually addedin the form of the dimer which is believed to form the monomeric1-nitro-2-nitrosoalkane before it reacts with the mineral acid.

Examples of suitable l-nitroalkanes for use as charge stocks in theprocess of this invention include, but are not limited to:

bis( 1-nitro-2-nitroso butane) bis( 1-nitro-2-nitroso hexane);

bis( l-nitro-1-ethyl-2-nitroso pentane); bis( l-nitro-2-nitroso-3-methyloctane) bis( 1-nitro-2-nitroso decane) bis( 1-nitro-2-nitroso dodecane)bis 1-nitro-2-nitroso hexadecane) bis( 1-nitro-2-nitroso eicosane); bis(1-nitro-2-nitroso pentacosane) l-nitro-2-nitroso butane;1-nitro-2-nitroso hexane; l-nitro-l-ethyl-Z-nitroso pentane;1-nitro-2-nitr0so-4-methy1 octane; l-nitro-2-nitroso decane;1-nitro-2-nitroso dodecane; 1-nitro-2-nitroso hexadecane;1-nitro-2-nitroso eicosane; l-nitro-Z-nitroso pentacosane;l-nitrobutanone-Z oxime; 1-nitropentanone-2 oxime; l-nitrohexanone-Zoxime; 1-nitro-4-methyloctanone-2 oxime; l-nitrododecanone-Z oxime; and1-nitropentacosanone-2 oxime.

The l-nitroalkane defined above is converted to a fatty acid amidehaving one less carbon atom than the monomeric form of the l-nitroalkanecharge stock by reaction with an anhydrous mineral acid selected fromthe group consisting of sulfuric and phosphoric. Weak acids, such asacetic, do not serve to convert the charge stocks of this invention tofatty acid amides.

By sulfuric acid is meant sulfuric acid having an H 80 content of 100percent and fuming sulfuric acid (oleum) which consists of a solution ofS03 in 100 percent sulfuric acid. The 100 percent sulfuric acid issometimes referred to as the monohydrate since it comprises one moleculeof S combined with one molecule of water. The sulfuric acid which issuitable for use in the process 0 i this invention, therefore, has amolar ratio of 50 to water from 1:1 to about 1.5:1 or more. The weightpercent S0 in 100 percent H 80 is about 81.5. The weight percent SO inthe sulfuric acid which is suitable for use in this invention is from81.5 to about 87 percent, indicating the addition of from O to 40 weightpercent S0 to the 100 percent H SO The preferred sulfuric acid is thecommercially available oleum which contains about 20 weight percentadded S0 (a total anhydrous 50;; content of about 84.5 weight percent).

By phosphoric acid is meant any polyphosphoric acid well known in theart having an H O/P O; ratio of three or less. When the H O/P O ratio isthree, the polyphosphoric acid is orthophosphoric acid (H PO Theconcentrated phosphoric acids, where the H O/P O is less than three, canbe obtained by boiling the orthophosphoric acid or more simply by addingP 0 to orthophosphoric acid. Pyrophosphoric acid (H P O has an H O/P Oratio of two, and melting of pyrophosphoric acid produces a mixture ofpolyphosphoric acids having various H O/ P 0 ratios less than 3: 1. PureH PO contains 72.4 percent P O and the orthophosphoric acid is oily inappearance and is viscous. As the weight percent of P 0 is increased,the polyphosphoric acids become more viscous, and in the range of 82-89percent P 0 are so viscous as to resemble tar and talfy. When the weightpercent P 0 is 4 of the amides to fatty acids in the presence of thestrong mineral acids.

The reaction of the 1 nitroalkane charge stocks defined above with thestrong mineral acids produces the desired fatty acid amides. Inaddition, gaseous by-products, such as CO and nitrogen, are formed andare evolved during reaction. Further, a complex is believed to be formedbetween the mineral acid and the amide product,

this requiring the presence of molar amounts of the strong above 90, thepolyphosphoric acid is a brittle glass. In

order to maintain a workable reaction medium, therefore, the phosphoricacid should have from 72.4 to about 86 percent P 0 Phosphoric acidcontaining higher amounts of P 0 can be used only with considerableamounts of solvent. In fact, it is preferred to utilize an inert solventin all cases with phosphoric acid in order to reduce the viscosity ofthe reaction medium and for other reasons given below.

The inert solvent can be any material which does not enter into areaction with either the l-nitroalkane charge stock or products andwhich does not enter into reaction with the mineral acid. The preferredinert solvents are the lower alkyl fatty acids having from one to threecarbon atoms, such as formic, acetic and propionic acids.

The purpose of the solvent is to allow for greater temperature controlin the reaction medium when forming the fatty acid amide (which is ahighly exothermic reaction) and to increase the solubility of theorganic charge stock and products in the reaction medium. In addition,as noted above, phosphoric acid is a viscous material and the use of asolvent reduces the viscosity of the polyphosphoric acid to a moreworkable range.

When a solvent is employed, the concentration of the strong mineralacid, calculated as the 100 percent mineral acid, in the reaction mediumcan suitably be as low as five weight percent and is preferably between25 and 95 weight percent, more preferably between and 80 weight percentof the l-nitroalkane free reaction medium.

The reaction medium comprising the strong mineral acid and, in addition,preferably a lower alkyl fatty acid solvent shouldbe substantiallyanhydrous in order to obtain high selectivity to the formation of thedesired fatty acid amides for the presence of water promotes hydrolysismineral acid to get substantially complete reaction of the charge stock.

The molar ratio of the strong mineral acid, calculated as the percentmineral acid, to the l-nitroalkane charge stocks, based on the monomericform of the charge stock, is suitably from about 1:1 to 50:1 with thepreferred molar ratios from about 1.5:l to 5:1. The range of molarratios given above based on the dimeric bis(l-nitro-2 nitrosoalkanes)would, of course, be doubled. The l-nitroalkane charge stocks and thefatty acid amide products are soluble in the strong mineral acid but, asnoted above, the use of organic solvents such as the lower alkyl fattyacids serve to increase the ease of solubilizing the charge stocks andproducts in the reaction medium.

The reaction temperature is not critical, but it is desired toetfectuate the conversion of the l-nitroalkanes to the desired fattyacid amides as quickly as possible and in turn to remove the fatty acidamide from the reaction medium as quickly as possible to avoid anysubsequent conversion of the amides in the strong acid to undesiredby-products. Suitable reaction temperatures are from 60 to 160 C. andthe preferred temperatures are between 80 and C. At temperatures lessthan about 60 C. the reaction is somewhat slower than is desired, whiletemperatures above C. promote decomposition of the product.

The reaction pressure is also not critical, but atmospheric pressureoperation is preferred for equipment simplification reasons. Thepressure should, of course, be sufiicient to maintain the reactants inthe liquid phase. Thus, if the higher temperature operation is desired,pressurized equipment may be necessary to maintain the solvent in theliquid phase if a solvent is employed. A suitable range of operatingpressures is between 0 and 100 p.s.i.g. or more, but atmosphericpressure is preferred.

The reaction of the l-nitroalkane charge stocks defined above to formthe fatty acid amides is very fast under the defined reactionconditions. Under the preferred temperature conditions the reaction issubstantially com plete within one to five minutes after contacting the1- nitroalkane with the strong mineral acid. At the higher reactiontemperatures the reaction time can be as short as one or two seconds.Even at the lower reaction temperatures of about 60 C. the reactionwould be substantially completed in 10 to 30 minutes. It is, of course,highly undesirable to maintain materials in contact with strong mineralacids for extended periods of time, especially at elevated temperatures,for obviously the acids will continue to attack the organic materials toproduce unwanted by-products and thus decrease the yield of the desiredfatty acid amides. It is therefore preferred to separate the fatty acidamide from the reaction medium as quickly as possible after it isformed. Any suitable means can be used to separate the fatty acid amide,and one suitable means involves the dilution of the reaction productwith a sufficient amount of cold water to result in the formation of aseparate organic phase. The strong acid catalyst will, of course, passinto the aqueous phase. The organic phase, containing the desired fattyacid amide, can be removed for further separation and purification.

It is further preferred that the reaction product be cooled before it isadmixed with the cold water, ice, iceacetic acid mixtures, etc. in orderto slow down further reactions of the fatty acid amide with the strongmineral acid. For example, as noted above, the acid amides are subjectto hydrolysis in the presence of aqueous mineral acids to produceorganic acids. This further reaction can be minimized by performing theamide separation by Water dilution at as low a temperature as possibleand in as short a time as possible. It is theerfore preferred to recoverthe fatty acid acide at a temperature less than about 50 C., and morepreferably at a temperature between and 35 C.

As noted above, the reaction of the l-nitroalkanes to form the desiredfatty acid amides is very fast and because of secondary reactions it isimportant to separate the amide product from the strong mineral acid asquickly as possible. It is also important that the concentration of thel-nitroalkane charge stock in the strong mineral acid be kept relativelylow in order to avoid sudden temperature rises with a consequentpromotion of undesired side reactions, such as polymer formation, and inthe production of large amounts of gaseous products which tend towardsexplosive reactions in closed reaction vessels. If means could beprovided for controlling the exothermicity of the reaction, then themethod of contacting the charge stock and strong mineral acid would notbe important. It has been found, however, that admixing al-nitro-Z-nitrosoalkane with anhydrous sulfuric acid at room temperaturein a 1:1 molar ratio and then slowly increasing the reaction temperatureresults in localized overheating as reaction proceeds with theproduction of unwanted tarry products and can lead to an undesiredrunaway reaction rather than to the desired fatty acid amides. It ispreferred to add the l-nitroalkane charge stock to a reaction mediumcomprising the anhydrous strong mineral acid which is maintained withinthe desired temperature range. It is further preferred that the reactionmedium contain, in addition, the quantity of solvent defined above, andthat the charge stock also suitably be dissolved in a sufiicient amountof the inert solvent to allow it to be more easily added to the reactionmedium.

It is also possible, although not preferred, to preheat thel-nitroalkane-inert solvent mixture before its addition to the strongmineral acid. If preheating is desired at this point, the temperature ofpreheat should be kept relatively low, for example, at a temperature ofbetween 50 and 60 C. since the l-nitroalkane charge stocks tend tothermally decompose to nitroolefins as they are heated to elevatedtemperatures.

A continuous type of operation is also possible by, for example, theconcurrent addition of the l-nitroalkane and the strong mineral acid atreaction temperatures to a reaction zone such as a coil reactor wherethe acid and reactants come into contact for the desired amount of timeand are then passed into a separation zone where the fatty acid amideproducts are separated by any suitable means such as those describedabove.

The invention will be further described with reference to the followingexperimental work.

In all of the runs, unless otherwise indicated, the lnitroalkane chargestock was added to the mineral acid Which had been previously heated tothe desired reaction temperature. The reaction products were cooled byindirect cooling to C. before being poured over crushed ice. The organiclayer was separated and extracted with diethylether. After evaporationof the ether the organic product was analyzed by gas liquidchromatography.

EXAMPLE 1 In the run for this example, 28 millimoles ofl-nitrohexanone-2 oxime was added over a period of 15 to minutes to areaction pot containing 625 millimoles of phosphoric acid (8284 percentby weight P 0 i.e. commercially available polyphosphoric acid). Thephosphoric acid was preheated to a temperature of 120 C. and thereaction pressure was atmospheric. After the addition of the oxime withvigorous stirring, the reaction temperature was maintained for fixeminutes after which time the product was cooled, poured over ice andextracted with ether, and the organic product after the ether wasevaporated was analyzed by gas liquid chromatography. Only valeramidewas found as a reaction product. No valeric acid or other monomericproducts were noted.

EXAMPLE 2 In the run for this example, a mixture of ten grams ofbis(1-nitro-2-nitroso decane) and 30 grams of glacial acetic acid washeated to C. for five minutes to convert the bis(1-nitro-2-nitrosodecane) into the isomeric 1-nitrodecanone-2 oxime. The resultingsolution of the nitroalkanone oxime in acetic acid was added slowly overa 20 minute period to a solution of 50 grams of the same phosphoric acidas used in Example'l in 50 grams of glacial acetic acid at C. (reflux).The weight percent phosphoric acid, calculated as orthophosphoric acid,in the initial reaction medium was about 31 percent. Heating wascontinued after the completion of the addition at reflux for anadditional ten minutes. The organic product was recovered by theprocedure indicated above and was then analyzed by gas liquidchromatography. The organic product was too high boiling for analysis.The organic product was then mixed with ten milliliters of concentratedhydrochloric acid and heated to reflux for two hours to convert anypelargonamide present to pelargonic acid. After separation of theorganic product from the aqueous acid the product was again analyzed bygas liquid chromatography. Comparison of the two gas liquidchromatographic analyses indicated only a trace of pelargonic acid inthe original product before treatment with the hydrochloric acid, whilethe hydrolyzed product contained mainly pelargonic acid. Whilepelargonamide was not observed in the chromatography due to its lowvolatility, the analysis indicates that the original product wassubstantially all pelargonamide.

EXAMPLE 3 Example 2 was repeated except 100 grams of acetic acid wereused in the initial reaction medium. Thus, the weight percent phosphoricacid, calculated as orthophosphoric acid, in the initial reaction mediumwas about 20 percent. Substantially the same results were obtained as inExample 2.

A comparison of Examples 1, 2 and 3 shows that phosphoric acid can beused neat or in dilution in a fatty acid (acetic acid) to result in theformation of the desired acid amides.

EXAMPLE 4 Example 1 was repeated except 50 grams of 20 percent oleum wassubstituted for the phosphoric acid. The analytical results againindicated the original product was sub stantially all valeramide.

A comparison of Examples 1 and 4 shows that sulfuric and phosphoricacids are substantially equivalent for the subject reaction.

Resort may be had to such variations and modifications as fall withinthe spirit of the invention and the scope of the appended claims.

I claim:

1. A process for the preparation of a fatty acid amide having from 2 to24 carbon atoms which comprises reacting at least one l-nitroalkanehaving from 3 to 25 carbon atoms selected from the group consisting of al-nitro- 2-nitrosoalkane having a hydrogen atom on the beta carbon atomand a 1-nitroalkanone-2 oxime with a mineral acid selected from thegroup consisting of sulfuric and phosphoric acids in an anhydrousreaction medium comprising said mineral acid under reaction conditionsincluding a temperature of from 60 C. to C.

2. A process according to claim 1 wherein the molar ratio of the mineralacid to said l-nitroalkane is at least about 1:1.

3. A process for the preparation of a fatty acid amide having from 2 to24 carbon atoms which comprises:

adding a l-nitroalkane selected from the group consisting ofl-nitroalkanes having the formula:

where R is a saturated alkyl radical having from 1 to 23 carbon atoms toan anhydrous reaction medium comprising a mineral acid selected from thegroup consisting of sulfuric and phosphoric acids at a ratesubstantially equal to the rate of reaction of said l-nitroalkane whilethe reaction medium is maintained at a temperature from 60 C. to 160 C.for a time between one second and 30 minutes and thereafter recoveringsaid fatty acid amide.

4. A process according to claim 3 wherein said reaction medium alsocontains a fatty acid solvent having from one to three carbon atoms.

5. A process according to claim 4 wherein the mineral acid is phosphoricacid and the fatty acid solvent is acetic acid.

6. A process according to claim 4 wherein the fatty acid amide isrecovered by dilution of the reaction product with a sufficient amountof cold water to result in the formation of an aqueous mineral acidphase and a separate organic phase, separating said organic phase fromsaid aqueous mineral acid phase and recovering the amide from theorganic phase.

References Cited UNITED STATES PATENTS 3,369,017 2/1968 Duynstee et al.260561 2,867,669 1/1959 Burkhard et a1 260-644 3,379,710 4/1968 Ellis260143 OTHER REFERENCES Brown, Jr., The I. R. Spectra of Intro etc.;cited by applicant.

Hornke et al., Name Reaction in Org. Chem. (1965) CA p. 63 13132 (1965).

Donaruma et al., The Prep of Amides From Salts, etc.; (1956) J. Org.Chem, 21, pp. 965-67 (1956).

Royals, The Beckmann Rearrangement, 6), Adv. Org. Chem. (1956), pp.608-609.

Chachaty et al., E.P.R. Spectra of Radicals Formed etc. (1967) CA 67 p.5581 No. 59390p. (1967).

LEWIS GOTTS, Primary Examiner G. HOLLRAH, Assistant Examiner US. Cl.X.R. 260-5 61 @2 3 UNITED STATES PATENT OFFICE CERTIFICATE 0F CORRECTIONPatent No. 3,562,302 Dated February 1971 Inventor(s) Alan F. Ellis It iscertified that error appears in the above-identified patent and thatsaid Letters Patent are hereby corrected as shown below:

Column 1, lines 52-55, the formula reading NOH H NOH H u R C C NO shouldread R C C NO Column 2 line 12 "volume 9 should read volume 79 Column 2line 52 "bis (l-nitro-2nitroso3methyl octar should read bis(l-nitro-2-nitroso-4-methyl octane Column 5 line 3 "theerfore" shouldread therefore Column 7 lines 8l2 the formula reading N=O H N-OH H I I IR C C NO should read R C C NO Signed and sealed this 13th day of July1971.

(SEAL) Attest:

WILLIAM E. SCHUYLER,

EDNARD M.F'LETCHER,JR.

Commissioner of Paten' Attesting Officer

